Although the relationship between autoimmunity and microorganisms is complex, there is evidence that microorganisms can prevent the development of various autoimmune diseases. Lactobacilli are beneficial gut bacteria that play an important role in immune system development. The goals of this study were to assess the ability of three different strains of lactobacilli (L. casei B255, L. reuteri DSM 17509 and L. plantarum LP299v) to control lupus development/progression in (NZBxNZW)F1 (BWF1) lupus-prone mice before and after disease onset, and identify the mechanisms mediating protection. BWF1 mice fed with individual L. casei or L. reuteri before disease onset exhibited delayed lupus onset and increased survival, while feeding L. plantarum had little impact. In vitro treatment of BWF1 dendritic cells with individual lactobacilli strains upregulated IL-10 production to various extents, with L. casei being the most effective. The protection mediated by L. casei was associated with upregulation of B7-1 and B7-2 by antigen presenting cells, two costimulatory molecules important for regulatory T cell (Treg) induction. Moreover, feeding L. casei lead to increased percentages of CD4⁺Foxp3⁺ Tregs and IL10-producing T cells in the lymphoid organs of treated mice. More importantly, mice fed L. casei after disease onset remained stable for several months, i.e. exhibited delayed anti-nucleic acid production and kidney disease progression, and increased survival. Therefore, feeding lactobacilli appears to delay lupus progression possibly via mechanisms involving Treg induction and IL-10 production. Altogether, these data support the notion that ingestion of lactobacilli, with immunoregulatory properties, may be a viable strategy for controlling disease development and progression in patients with lupus, i.e. extending remission length and reducing flare frequency.

尽管自身免疫与微生物之间的关系很复杂，但是有证据表明微生物可以预防各种自身免疫性疾病的发展。乳酸杆菌是有益的肠道细菌，在免疫系统发育中起重要作用。这项研究的目的是评估三种不同菌株的乳酸杆菌（干酪乳杆菌B255，罗伊氏乳杆菌DSM 17509和植物乳杆菌LP299v）控制狼疮易发性（NZBxNZW）F1（BWF1）的能力。小鼠在疾病发作前后，并找出介导保护作用的机制。用个体干酪乳杆菌或罗伊氏乳杆菌喂养的BWF1小鼠在疾病发作之前表现出狼疮发作延迟和存活增加，而饲喂植物乳杆菌的影响很小。用单个乳杆菌菌株体外处理BWF1树突状细胞在不同程度上上调了IL-10的产生，其中干酪乳杆菌是最有效的。干酪乳杆菌介导的保护作用与抗原呈递细胞对B7-1和B7-2的上调有关，抗原呈递细胞是两个对调节T细胞（Treg）诱导重要的共刺激分子。此外，饲喂干酪乳杆菌可导致治疗小鼠淋巴器官中CD4 ⁺ Foxp3 ⁺ Tregs和产生IL10的T细胞百分比升高。更重要的是，老鼠喂食干酪乳杆菌在疾病发作后保持稳定数月，即表现出延迟的抗核酸产生和肾脏疾病进展，并增加了存活率。因此，喂养乳杆菌似乎可能通过涉及Treg诱导和IL-10产生的机制延迟狼疮的进展。总而言之，这些数据支持以下观点：摄入具有免疫调节特性的乳酸杆菌可能是控制狼疮患者疾病发展和进展的可行策略，即延长缓解期并减少发作频率。